Founded in 2021, biotech startup Colossal Biosciences has swiftly introduced the concept of de-extinction to the world with its revolutionary uses of genomic sequencing and CRISPR gene editing technology to revitalize lost icons like the woolly mammoth, dodo, and Tasmanian tiger.
The company continues to make significant breakthroughs in the de-extinction space, including recently announcing the creation of elephant stem cells — a crucial step in making the edits necessary to create a mammoth-elephant hybrid cell line.
While Colossal Biosciences is moving quickly toward its goal of rewilding the first mammoth hybrid calves by 2028, de-extinction has proven to be a meticulous process, requiring novel technologies and gene editing techniques to ensure the proper gestation and survival of calves as well as the creation of a hybrid species that heavily resembles the mammoth in appearance and ecological functionality.
As with most projects, some steps on the de-extinction path have been more difficult than others, and editing the Asian elephant’s cell line with crucial tundra-suited genes like thick hair and fat reserves was one especially daunting task given the billions of letters of DNA encased in the mammoth’s genome: enough letters to write 6,888 books.
Colossal Biosciences quickly realized that sifting through a mammoth’s genetic code in search of specific genes was no task for a human. That’s why the company launched Form Bio in 2022, an independent spinout company providing a software that transforms the scientific computational process.
“Form Bio is the missing piece in scientific discovery,” Ben Lamm, Colossal co-founder and CEO, said in a press release. “When you have a big scientific endeavor like de-extincting a species, you not only need the smartest scientists in the world, you need powerful software, much of which simply hasn’t existed until now.
“After reviewing everything available on the market, we chose to create our own software solution. Now, we want to share this modern, comprehensive platform with the broader community to impact other areas of scientific innovation, including human health.”
Co-founded by Lamm and former Colossal executives Kent Wakeford and Andrew Busey, Form Bio provides a platform that streamlines the work of synthetic biologists. Powered by artificial intelligence, the software manages and analyzes large datasets, visualizing results and creating simplified workflows that enable collaboration among peers.
Colossal Uses for a New Formed Computational Software
Since developing Form Bio in 2022, Colossal Biosciences has used the software to augment its invaluable conservation and de-extinction work.
“Form Bio helps Colossal’s biology teams save time and maximize our research in ways we didn’t realize were possible,” said Eriona Hysolli, Ph.D., Colossal’s head of biological sciences, on Form Bio’s website.
Not only has the platform aided the genomic sequencing of extinct species like the woolly mammoth, it has also been used to inform gene edits key to restoring diversity into critically endangered species, a process known as genetic rescue.
In 2023, Colossal Biosciences used Form Bio to conduct a comparative analysis between the DNA and genomes of the northern white rhino and its sister taxon, the southern white rhino. The northern white rhino has been the subject of large-scale breeding programs and genetic rescue efforts as the subspecies is down to its last two individuals: a related pair of females named Najin and Fatu.
By performing this comparative analysis, Form Bio is helping to identify genetic diversity missing in the northern white rhino that has provided its southern counterpart (with a population of over 20,000) such success. Once identified, Colossal Biosciences can again use Form Bio’s software to determine what genetic edits would best confer diversity in the subspecies.
“Can we [use Form Bio to] identify what are the targets that we need to actually go after and edit and engineer? The answer is absolutely yes, and we’ve gotten very good at selecting impactful genetic differences,” said Hysolli.
AAV Advancements
In addition to advancing Colossal’s work with extinct and endangered species, Form Bio’s software has widespread applications for adeno-associated virus gene therapies. It can accelerate the development of potentially life-saving medications.
“As a Form Bio customer, we are thrilled with the uniquely valuable AI-driven insights they’ve contributed to our research and development efforts,” said Jenny Marlow, Ph.D., the chief scientific officer of gene therapy company Solid Biosciences, on Form Bio’s website.
“By working closely with this world-class team and cutting-edge technology, we can clearly see that applying innovative AI solutions to preclinical cell and gene therapy development offers exciting potential for [cell and gene therapy] companies’ economics, market timing, and ability to impact human health.”
Form Bio offers a robust toolkit for companies developing crucial gene therapies. Along with providing a list of preclinical predictions such as detailed drug product characterizations, multicandidate comparisons, bioreactor simulations, gene expression predictions, immunotoxicity analyses, and candidate optimizations, Form Bio has partnered with Ginkgo Bioworks to test these predictions.
A biotechnology company focused on the genetic engineering of microbes, Ginkgo Bioworks offers cell programming that further accelerates the development of AAV therapies, providing an integrated system to bring Form Bio’s work to life.
“Ginkgo’s gene therapy platform is focused on capsid engineering, payload engineering, and AAV production. Our AI-optimized designs fit right into their engineering and production, whether just their engineering work or their existing capsid and/or AAV production host cell lines,” said Form Bio CEO Wakeford.
Forming a Solution
At a time when innovation in synthetic biology is leading the development of unique conservation strategies and lifesaving AAV gene therapies, Form Bio’s loosening of computational burdens has fostered solutions for the Earth’s most pressing issues.
As Colossal Biosciences continues to leverage Form Bio for its critical projects, the software continues to be a testament to the benefits of AI-augmented science. With the ever-evolving nature of Form Bio, there’s truly no telling where the platform will take us in the future.
“Form Bio is a critical addition to both our public and private arsenals,” stated film producer and lead investor Thomas Tull. “With innovative software that sits at the intersection of biology and discovery and enables scientists to collaborate with greater ease, Form Bio is another proof point of Colossal’s ability to apply breakthrough technologies to make incredible scientific and technological advances.”